The overall goal of this research program is to develop novel methodologies with enhanced sensitivity for use in evaluating visual function, assessing the efficacy of therapeutic interventions, and providing new insight into the underlying causes of vision loss in ocular diseases. The goal of this proposal is to identify the mechanisms that form the basis for the spatial contrast sensitivity deficits observed in patients with retinitis pigmentosa (RP), a group of hereditaty retinal degenerations that are that are the most common genetic cause of blindness in adults. This goal Will be achieved by completing two specific aims: Aim 1 is to develop a computerimplemented vlsual-riolse-based testing strategy. Visual-noise-based techniques can provide more information than standard clinical tests because perfomnance is factored into the components that govern contrast sensitivity. However, several issues regarding visual-noise-based approaches have been identified in pilot work that must be resolved. Aim 2 will apply the novel testing strategy to individuals with RP to test three distinct, non-mutually exclusive hypotheses regarding tiie factors underlying their contrast sensitivity losses: patients with RP have elevated levels of additive noise within the visual pathway, patients with RP have elevated levels of multiplicative noise within the visual pathway, or patients with RP have an Inability to extract signal information from the noise. In addition to providing a better understanding ofthe source of contrast sensitivity losses In patients with RP, this research will yield a sensitive technique that will be useful for evaluating the efficacy of future therapeutic interventions in a variety of ocular disorders. The development of more sensitive metfiods of assessing visual function, such as that proposed here, is becoming increasingly important as gene-directed therapies and retinal cell transplantation therapies begin to enter clinical trials.